- This revised application focuses on the role of EGFR ligands and the related growth factors, neuregulins, and their receptors (erbB2, erbB3, erbB4) in skin biology. The premise on which the proposal is based is that crosstalk between different ligand and receptor species could amplify or diversify their signal transduction pathways and thus modulate their impact on these processes. The specific aims are to: 1) Determine which members and forms of the EGF family of ligands and receptors are active in normal and injured skin; 2) examine ligand-dependent interactions between erbB receptors in skin and their effects on signal transduction and cellular behavior in vitro, and 3) evaluate in interference with EGFR and erbB2 signaling in skin in dominant-negative receptor transgenic mice expressing a kinase-deleted form of erbB2, compromise skin development or epidermal wound healing in transgenic mice.